[unreadable] The discovery of the biaryl pyrazole SR141716, a potent CB1 receptor antagonist with nanomolar affinity, provides a unique chemical tool for further characterization of the cannabinoid pharmacophore in its relationship to the binding domain of cannabinoid antagonists. In the first two years of my postdoctoral training at Research Triangle Institute, I synthesized amide and hydrazide analogues of SR141716. I now propose to further characterize these compounds as antagonist or inverse agonists in several signal transduction pathways. They will be tested in the adenylate cyclase, mitogen-activated protein (MAP) kinase and nitric oxide (NO) activation assays using two different cell lines: mouse N18TG2 neuroblastoma cells and Chinese hamster ovary (CHO) cells transfected with the human CB1 receptor, utilizing the following three cannabinoid agonists: CP55940, WIN 55212-2, and (R)-(+) methanandamide. By determining how these compounds affect signal transduction pathways, a better understanding of the pharmacology of biaryl pyrazole compounds will be gained in order to improve on their potential use as therapeutic agents. [unreadable] [unreadable] [unreadable] [unreadable]